Structural highlights
Function
[SEC4_YEAST] Involved in exocytosis. Maybe by regulating the binding and fusion of secretory vesicles with the cell surface. The GTP-bound form of SEC4 may interact with an effector, thereby stimulating its activity and leading to exocytotic fusion. SEC4 may be an upstream activator of the 19.5S SEC8/SEC15 particle. SEC4 probably interacts directly with SEC8; it could serve as the attachment site for the SEC8/SEC15 particle.[1] [SEC2_YEAST] Guanine nucleotide exchange factor for SEC4, catalyzing the dissociation of GDP from SEC4 and also potently promoting binding of GTP. Activation of SEC4 by SEC2 is needed for the directed transport of vesicles to sites of exocytosis. Binds the Rab GTPase YPT32, but does not have exhange activity on YPT32.[2] [3] [4]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Vesicular transport during exocytosis is regulated by Rab GTPase (Sec4p in yeast), which is activated by a guanine nucleotide exchange factor (GEF) called Sec2p. Here, we report the crystal structure of the Sec2p GEF domain in a complex with the nucleotide-free Sec4p at 2.7 A resolution. Upon complex formation, the Sec2p helices approach each other, flipping the side chain of Phe-109 toward Leu-104 and Leu-108 of Sec2p. These three residues provide a hydrophobic platform to attract the side chains of Phe-49, Ile-53, and Ile-55 in the switch I region as well as Phe-57 and Trp-74 in the interswitch region of Sec4p. Consequently, the switch I and II regions are largely deformed, to create a flat hydrophobic interface that snugly fits the surface of the Sec2p coiled coil. These drastic conformational changes disrupt the interactions between switch I and the bound guanine nucleotide, which facilitates the GDP release. Unlike the recently reported 3.3 A structure of the Sec4p.Sec2p complex, our structure contains a phosphate ion bound to the P-loop, which may represent an intermediate state of the nucleotide exchange reaction.
Crystal structure of the Sec4p.Sec2p complex in the nucleotide exchanging intermediate state.,Sato Y, Fukai S, Ishitani R, Nureki O Proc Natl Acad Sci U S A. 2007 May 15;104(20):8305-10. Epub 2007 May 8. PMID:17488829[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Grosshans BL, Andreeva A, Gangar A, Niessen S, Yates JR 3rd, Brennwald P, Novick P. The yeast lgl family member Sro7p is an effector of the secretory Rab GTPase Sec4p. J Cell Biol. 2006 Jan 2;172(1):55-66. PMID:16390997 doi:http://dx.doi.org/10.1083/jcb.200510016
- ↑ Walch-Solimena C, Collins RN, Novick PJ. Sec2p mediates nucleotide exchange on Sec4p and is involved in polarized delivery of post-Golgi vesicles. J Cell Biol. 1997 Jun 30;137(7):1495-509. PMID:9199166
- ↑ Elkind NB, Walch-Solimena C, Novick PJ. The role of the COOH terminus of Sec2p in the transport of post-Golgi vesicles. J Cell Biol. 2000 Apr 3;149(1):95-110. PMID:10747090
- ↑ Ortiz D, Medkova M, Walch-Solimena C, Novick P. Ypt32 recruits the Sec4p guanine nucleotide exchange factor, Sec2p, to secretory vesicles; evidence for a Rab cascade in yeast. J Cell Biol. 2002 Jun 10;157(6):1005-15. Epub 2002 Jun 3. PMID:12045183 doi:http://dx.doi.org/10.1083/jcb.200201003
- ↑ Sato Y, Fukai S, Ishitani R, Nureki O. Crystal structure of the Sec4p.Sec2p complex in the nucleotide exchanging intermediate state. Proc Natl Acad Sci U S A. 2007 May 15;104(20):8305-10. Epub 2007 May 8. PMID:17488829
